What is the recommended use and dosage of alirocumab (Praluent) for patients with high cardiovascular risk?

Alirocumab (Praluent) for High Cardiovascular Risk Patients

Alirocumab is indicated for adults with established cardiovascular disease to reduce myocardial infarction, stroke, and unstable angina requiring hospitalization, and as adjunctive therapy for primary hyperlipidemia including heterozygous familial hypercholesterolemia when LDL-C remains elevated despite maximally tolerated statin therapy. 1

Recommended Dosing

Adults with Established ASCVD or Primary Hyperlipidemia

• Starting dose: 75 mg subcutaneously every 2 weeks OR 300 mg every 4 weeks 1
• If LDL-C response is inadequate, increase to 150 mg every 2 weeks 1
• The 75 mg every 2 weeks dose reduces LDL-C by approximately 45%, while 150 mg every 2 weeks achieves approximately 58% reduction when added to maximally tolerated statin therapy 2

Patients with HeFH Undergoing Apheresis or HoFH

• Recommended dose: 150 mg every 2 weeks 1
• Can be administered without regard to timing of LDL apheresis 1

Pediatric Patients (≥8 years) with HeFH

• Body weight <50 kg: 150 mg every 4 weeks (may increase to 75 mg every 2 weeks if inadequate response) 1
• Body weight ≥50 kg: 300 mg every 4 weeks (may increase to 150 mg every 2 weeks if inadequate response) 1

Clinical Efficacy Evidence

Cardiovascular Outcomes

The ODYSSEY OUTCOMES trial demonstrated that alirocumab reduces major adverse cardiovascular events by 15% (HR 0.85,95% CI 0.78-0.93, P<0.001) over 2.8 years in patients with recent acute coronary syndrome. 3

• The composite primary endpoint (death from CHD, nonfatal MI, fatal/nonfatal ischemic stroke, or unstable angina requiring hospitalization) occurred in 9.5% of alirocumab patients versus 11.1% of placebo patients 3
• Patients with diabetes showed greater absolute risk reduction (2.3%) compared to those with prediabetes (1.2%) or normoglycemia (1.2%) 3

LDL-C Reduction

• Alirocumab reduces LDL-C by 36-59% when added to maximally tolerated statin therapy 3
• In patients with heterozygous familial hypercholesterolemia, alirocumab achieves ≥50% additional LDL-C reduction 3
• LDL-lowering effects can be measured as early as 4 weeks after initiation 1

Patient Selection Criteria

Primary Indications

Alirocumab should be added to maximally tolerated statin plus ezetimibe in the following scenarios:

• Established ASCVD with LDL-C ≥70 mg/dL despite maximally tolerated statin and ezetimibe 4
• Heterozygous familial hypercholesterolemia (ages 30-75 years) with LDL-C ≥100 mg/dL despite maximally tolerated statin and ezetimibe 3, 4
• Severe primary hypercholesterolemia (baseline LDL-C ≥220 mg/dL) with LDL-C ≥130 mg/dL despite maximally tolerated statin and ezetimibe 3

High-Risk Features Supporting Use

• Multiple major ASCVD events (recent ACS, history of MI, ischemic stroke, symptomatic PAD) 4
• Age ≥65 years, diabetes, hypertension, CKD, current smoking, or persistently elevated LDL-C ≥100 mg/dL 4

Treatment Goals

Target LDL-C <55 mg/dL (1.4 mmol/L) with ≥50% reduction from baseline for patients with established ASCVD 2

• For patients experiencing a second vascular event within 2 years while on maximally tolerated statin therapy, consider an even lower target of <40 mg/dL (1.0 mmol/L) 2

Monitoring and Dose Adjustment

• Assess LDL-C levels 4 weeks after initiating therapy 4
• For patients on 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dose, as levels can vary between doses 1
• Ensure patient adherence to statin and ezetimibe before adding alirocumab 4

Administration Instructions

• Administer subcutaneously into thigh, abdomen, or upper arm 1
• Allow to warm to room temperature for 30-40 minutes if refrigerated 1
• Rotate injection sites with each administration 1
• For 300 mg dose, give two consecutive 150 mg injections at different sites 1

Safety Profile

• Generally well-tolerated with adverse effects including nasopharyngitis, injection site reactions, and influenza 2
• Injection-site reactions occur more frequently with alirocumab versus placebo 5
• Treatment-emergent adverse events leading to permanent discontinuation occur in approximately 3% of patients 6

Critical Caveats

Ezetimibe should be tried before alirocumab due to lower cost and established safety profile 4

• Consider cost-effectiveness in decision-making, as PCSK9 inhibitors are significantly more expensive than other LDL-lowering therapies 4
• Combination therapy with statin plus fibrate or niacin is not recommended and does not improve ASCVD outcomes 3